Our aim was to investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Gonarthrosis (AMG). Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements. The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H&
E staining) and immunohistochemical analysis (Type I and II Collagen, proliferation and apoptosis). Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N. There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal). The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (p<
0.0001). There was no significant difference in the Collagen II content or gene expression between areas. The Collagen I immunohistochemistry showed increased staining within chondrocyte pericellular areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (p<
0.0001). Furthermore, real time PCR showed a significant increase in Collagen I expression in the macroscopically normal areas compared to the damaged areas (p=0.04). In AMG there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.
90% of lateral compartments were normal and none had full thickness cartilage loss. However 10% showed high signal in the tibial plateau. There was a highly reproducible pattern of osteophyte formation; 94% posteromedial and posterolateral aspect of medial femoral condyle; 90% medial tibial; 80% medial femoral and 84% lateral intercondylar notch.
The aim of this study was to define normal, borderline, and abnormal parameters for the morphology of the proximal femur, in the context of the cam deformity, by studying asymptomatic individuals with normal clinical examination and no osteoarthritis from the general population.
Despite the satisfactory short-term implant survivor-ship, there is an increasing concern that the metal-on-metal hip resurfacing arthroplasty (MoMHRA) release large amount of very small wear particles and metal ions. The periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. These were found be locally destructive, requiring revision surgery in most patients. It has been suggested that either an immune reaction or cytotoxic effect of chromium(Cr) or cobalt(Co) may play a role in its aetiology. However, the effect of the phagocytosis of implant-associated metal nanoparticles on macrophages has not been elucidated. The aim of this study was to investigate the in vitro viability and proliferative response of murine macrophages to clinically relevant metal nanoparticles and ions.
At the end of day 1 and 4, two methods were used to quantify cell proliferation and viability. The AlamarBlue assay(Invitrogen) incorporates a fluorimetric growth indicator and the fluorescence signal correlates with metabolic activity of the cells. LIVE/DEAD stain kit(Molecular Probes) contains two fluorescent dyes to stain living cells green and dead cells red. The viability was calculated by the number of live cells divided by total cell numbers. Inter-group comparisons were performed using one-way ANOVA with Tukey post hoc test. Differences at p<
0.05 were considered to be significant.
Recently, a series of locally destructive soft tissue pseudotumour has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA), requiring revision surgery in a high percentage of patients. Based on the histological evidence of lymphocytic infiltration, a delayed hypersensitivity reaction to nickel (Ni), chromium (Cr) or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of hypersensitivity reaction to metals in patients with pseudotumour.
Group 1: MoMHRA patients with pseudotumours, detected on the ultrasound and confirmed with MRI (n=6, 5 F:1 M, mean age 53 years); Group 2: MoMHRA patients without pseudotumours (n=13, 7 F:6 M, mean age 55 years); and Group 3: age-matched control subjects without metal implants (n=6, 4 F:2 M, mean age 54 years). Lymphocyte transformation tests (LTT) were used to measure lymphocyte proliferation responses to metals. Peripheral blood mononuclear cells were isolated from heparinized blood samples using standard Ficoll–Hypaque® (Pharmacia). The PBMC were cultured at a cell density of 106 cells/mL. Culture was set up in the presence of either:
medium alone; nickel chloride (Sigma; 10-4M-10-6M); cobalt chloride (10-4M-10-6M); and chromium chloride (10-4M-10-6M). After 5 days of culture, cells were pulsed with [3H]-thymidine and proliferation was assessed by scintillation counting. The stimulation index (SI) was calculated by the ratio of mean counts per minute of stimulated to unstimulated cultures. A SI value of greater than 2.0 was interpreted as a positive result.
Current intervention strategy is focussed on prevention of initial device colonisation and inhibition of genes encoding biofilm formation.
Determine the minimum inhibitory concentration (MIC) of betadine. Investigate the effect of betadine on icaADBC operon encoded staphylococcal biofilm formation. Investigate wether betadine can prevent bacterial adherence and biofilm formation by inhibition of the encoding genes.
Total RNA for cDNA synthesis was isolated from bacterial at different twofold dilutions of betadine concentrations. Real time polymerase chain reaction was used to quantify effects of betadine on gene expression pattern of the icaADBC operon using the constitutively expressed gyrB gene as internal control. Bacterial was cultivated on polystyrene plates coated with different sub-inhibitory and clinical in-use doses of betadine to assess surface adherence.
A step-wise reduction of biofilm was observed at increasing sub-inhibitory doses of betadine (p<
0.0001). IcaA expression correlated with biofilm formation in staphylococcal organisms. Decrease in icaA expression was strongly associated with an increase in expression in the biofilm repressor gene, icaR. The repressive effect of betadine on biofilm formation by Staphylococcal bacteria is by a separate mechanism from its bacteriostatic mechanism of action.
Prevention of bacterial surface attachment as demonstrated by this study is suggestive that these compounds could be developed as a surface coating agents for orthopaedic implants.
Tribological studies of hip arthroplasty suggest that larger diameter metal-on-metal (MOM) articulations would produce less wear than smaller diameter articulations. Other advantages using these large femoral heads implants include better stability with lower dislocation rates and improved range of motion. The aim of the present study was to compare chromium (Cr), cobalt (Co) and titanium (Ti) ion concentrations up to 1-year after implantation of different large diameter MOM total hip arthroplasty (THA).
Statistical group comparison revealed significant difference for Cr (p=0.006), Co (p=0.047) and Ti (p=<
0.001). With Biomet implants presenting the best results for Cr and Co and Zimmer the highest Ti level.
Metal on Metal Hip Resurfacing Arthroplasty (MoMHRA) has gained popularity due to its perceived advantages of bone conservation and relative ease of revision to a conventional THR if it fails. Known MoMHRA-associated complications include femoral neck fracture, avascular necrosis/collapse of the femoral head/neck, aseptic loosening and soft tissue responses such as ALVAL and pseudotumours. This study’s aim was to assess the functional outcome of failed MoMHRA revised to THR and compare it with a matched cohort of primary THRs.
Although many causes of FAI are described, the vast majority of patients give no history of previous hip disease. The purpose of this study was to investigate the extent to which FAI has an underlying genetic basis, by studying the siblings of patients undergoing surgery for FAI and comparing them with controls.
Patello-femoral instability (PFI) affects 40 individuals per 100,000 population and causes significant morbidity. The causes of patello-femoral instability are multi-factorial, and an isolated anatomical abnormality does not necessarily indicate instability. Patello-femoral subluxation ranges from 0% (stable patella tracking) to 100% (dislocation) and there is an established relationship between the amount of subluxation and anterior knee pain. Traditionally, magnetic resonance (MR) imaging and standard radiographs are used to guide the clinician towards a suitable corrective procedure for PFI. The multi-factorial nature of patello-femoral instability is not addressed with current imaging techniques. This study aims to address which anatomical variables assessed on MR images are most relevant to patello-femoral subluxation. This information will aid surgical decision making, particularly in selecting the most appropriate reconstructive surgery. A retrospective analysis of MR studies of 60 patients with suspected patello-femoral instability was performed. All patients were graded for degree of subluxation using a dynamic MR scan. The patient scans were assessed for the presence of a specific range of anatomical variables:
patella alta, (modified Insall-Salvatti) patella type (Wiberg classification) trochlea sulcus angles for bone and cartilage surfaces the distance of the vastus medialis obliquis (VMO) muscle from the patella trochlea and patella cartilage thickness the horizontal distance between the tibial tubercle and the midpoint of the femoral trochlea (TTD) patella engagement – the percentage of the patella height that is captured in the trochlea groove in full extension. The Wilk’s Lambda test for multi-variate analysis was used to establish whether any relationship was present between the degree of patello-femoral instability and bony or soft tissue anatomical variables. Non-parametric statistical tests were applied across the groups and within the groups to assess their relative significance. The following variables showed a significant relationship with patellofemoral subluxation; distance of the VMO from the patella (<
0.001), TTD (<
0.001), patella engagement (0.001), sulcus angles (0.004) and patella alta (0.005). This study agrees with previous work showing a significant correlation between subluxation and trochlea sulcus angle and TTD. This is the first study to establish a significant correlation between patella engagement and radiological instability. The lower the percentage engagement of the patella in the trochlea, the greater the degree of patello-femoral instability. Patella engagement showed a more significant relationship with subluxation than patella alta. We report a new method of predicting patello-femoral instability by measuring the overlap of the patella in the trochlea groove.
Participants were classified as:
Normal morphology, no clinical features Abnormal morphology, no clinical features Abnormal morphology, clinical signs but no symptoms Abnormal morphology with symptoms and signs Osteoarthritis.
100% of medial compartments showed full thickness anteromedial loss with preservation of the posteromedial cartilage. When present, the meniscus was extruded in 96% of cases. 90% of lateral compartments were normal and none had full thickness cartilage loss. However 10% showed high signal in the tibial plateau. There was a highly reproducible pattern of osteophyte formation; 94% posteromedial and posterolateral aspect of medial femoral condyle; 90% medial tibial; 80% medial femoral and 84% lateral intercondylar notch.
patients’ pre-operative demographics for age, weight, height, BMI, intraoperative variables such as the operating surgeon (n=2), insert and component sizes, and clinical assessment criteria including pre-operative and five-year post-operative Oxford knee (OKS) and Tegner (TS) scores.
Chondrocytes are responsible for the mechanical resilience of cartilage by controlling the synthesis/degradation of the extracellular matrix. In osteoarthritis (OA), increased activity of cytokines/degradative enzymes (e.g. IL-1beta, MMP-13) play a key role leading to matrix breakdown/cartilage loss. Studying early events in OA might identify targets for limiting the deleterious changes to cartilage stability. Human chondrocyte shape in situ is normally elipsoidal/spheroidal however abnormal forms within otherwise macroscopically normal cartilage are present. Changes to cell shape can alter ECM metabolism and thus these abnormal forms might be an early event in OA. We have investigated whether levels of IL-1beta and MMP-13 are altered in human chondrocytes of abnormal morphology. Tibial plateau cartilage was obtained from patients undergoing knee arthroplasty and only areas graded 0 or 0–1 studied. The shape of fluorescently-labelled in situ chondrocytes was classified by confocal scanning laser microscopy with cartilage depth, and cells characterised as normal (no cytoplasmic processes) or abnormal (one/more cytoplasmic process). Within grade 0 cartilage about 40% of the cells demonstrated abnormal morphology with a reduced proportion in deep zones. Fluorescence immunohistochemistry of antibodies for IL-1beta or MMP-13 was studied in the same cells and quantified. There was an increase in IL-1beta fluorescence with abnormal chondrocytes within the superficial (p=0.033; 21 joints >
190 cells) and deep zones (p=0.001; 8 joints >
100 cells). There were no differences between MMP-13 labelling of normal compared to abnormal chondrocytes within either the superficial or deep zones. Our results suggest that in relatively non-degenerate cartilage, a proportion of the chondrocyte population demonstrated abnormal morphology and that these cells have elevated levels of IL-1beta but not MMP-13. However, we do not know if chondrocyte shape alters cytokine levels, or vice versa. Additionally, the role of cartilage age is unclear, as although the cartilage samples were relatively normal they were obtained from aged individuals. Nevertheless these results show changes to chondrocyte morphology and increased levels of IL-1beta, and thus presumably matrix catabolism - in relatively normal human articular cartilage, raising the possibility that this is an early event in cartilage degeneration. Supported by the Wellcome Trust (075753).
Kinematic data from in-vivo fluoroscopy measurements during a step-up activity was used to determine the relative tibial-femoral position as a function of knee flexion angle for each model. Medial and lateral force distribution was adapted from loads measured in-vivo with an instrumented implant during a step-up activity. The affect that varying the bearing thickness has on the stresses in the bearing was investigated. In addition, varus-valgus mal-alignment was investigated by rotating the femoral component through 10 degrees.
Tibial lesion: In lateral OA, the midpoint of lesions was 2.0mm (SD:6.5) posterior to the reference line passing through the mid-coronal plane of the resected tibia. This was located significantly more posterior (p=0.038) than midpoint in medial OA, which was 2.2mm (SD:5.7) anterior to the reference line. Knee Flexion Angle: In lateral OA, the midpoint of lesions was on average at 40° flexion and sites of smaller lesions were very variable. The lesion expanded both anteriorly and posteriorly. In medial OA, smaller femoral lesions occurred in full extension and extended further posteriorly with disease progression. No significant difference was demonstrated in medial and lateral localisation of the lesions.
We report on a group of 20 metal-on-metal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms. We describe these masses as pseudotumours. All patients underwent plain radiography and fuller investigation with CT, MRI and ultrasound. Where samples were available, histology was performed. All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, an enlarging mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. Fourteen of the 20 cases (70%) have so far required revision to a conventional hip replacement and their symptoms have either settled completely or improved substantially since the revision surgery. Two of the three bilateral cases have asymptomatic pseudotumours on the opposite side. We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years after a hip resurfacing. The cause of these pseudotumours is unknown and is probably multi-factorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudotumours will increase.
The purpose of this study was to determine if a single physiotherapy intervention would enable patients to kneel following Unicompartmental knee arthroplasty (UKA). Kneeling is an important functional activity that is frequently not performed after knee arthroplasty, thus affecting a patient’s ability to carry out basic tasks of everyday life. There is however no clinical reason why patients should not kneel and many with proposed knee surgery ask about the possibility of kneeling after their operation. Sixty adults participated in a prospective randomised controlled trial with blinded assessments. At 6 weeks post-operatively UKA patients were randomised to either the Routine care group where no advice on kneeling was given or to the Kneeling intervention group where participants were taught and given advice on how to kneel and were encouraged to do so. They were re-assessed at 1 year. The primary outcome measure was Question 7 of the Oxford Knee Score which asks the question “Could you kneel down and get up again afterwards?” Pre-operatively there was no difference in the kneeling ability of the two groups. At 1 year the difference in kneeling ability between the two groups was highly significant (p<
0.05). Spearman’s correlation coefficient showed no significant association between a change in score of Question 7 at 1 year and the following factors; scar position, numbness, range of flexion, arthritic involvement of other joints and pain. Linear regression analysis also confirmed that these factors were not successful in predicting a change in kneeling ability. This study showed that the single factor predictive of kneeling ability was the physiotherapy intervention provided at 6 weeks post-operatively and it is suggested that kneeling should be incorporated into patient’s post-operative rehabilitation programmes.
revision surgery and poor functional outcome as the end-points.
The aim of this study was to investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Osteoarthritis of the Knee (AMOA). Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements. The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H&
E staining) and immunohistochemical analysis (Type I and II Collagen). Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N. There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal). The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (ANOVA P<
0.0001). There was no significant difference in the Collagen II content or gene expression between areas. The Collagen I immunohistochemistry showed increased staining within chondrocyte territorial areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (ANOVA P<
0.0001). Furthermore, real time PCR showed that there was a significant increase in Collagen I expression in the macroscopically normal areas (p=0.04). In AMOA there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.
This study reports a clinical comparison of new and old establishing whether this modified implant has maintained the established normal kinematic profile of the Oxford UKR.
Knee kinematics were assessed by analysing the movement of the femur relative to the tibia using the PTA.
Finite element (FE) analysis is widely used to calculate stresses and strains within human bone in order to improve implant designs. Although validated FE models of the human femur have been created (Lengsfeld et al., 1998), no equivalent yet exists for the tibia. The aim of this study was to create such an FE model, both with and without the tibial component of a knee replacement, and to validate it against experimental Results: A set of reference axes was marked on a cleaned, fresh frozen cadaveric human tibia. Seventeen triaxial stacked strain rosettes were attached along the bone, which was then subjected to nine axial loading conditions, two four-point bending loading conditions, and a torsional loading condition using a materials testing machine (MTS 858). Deflections and strain readings were recorded. Axial loading was repeated after implantation of a knee replacement (medial tibial component, Biomet Oxford Unicompartmental Phase 3). The intact tibia was CT scanned (GE HiSpeed CT/i) and the images used to create a 3D FE mesh. The CT data was also used to map 600 transversely isotropic material properties (Rho, 1996) to individual elements. All experiments were simulated on the FE model. Measured principal strains and displacements were compared to their corresponding FE values using regression analysis. Experimental results were repeatable (mean coefficients of variation for intact and implanted tibia, 5.3% and 3.9%). They correlated well with those of the FE analysis (R squared = 0.98, 0.97, 0.97, and 0.99 for axial (intact), axial (implanted), bending, torsional loading). For each of the load cases the intersects of the regression lines were small in comparison to the maximum measured strains (<
1.5%). While the model was more rigid than the bone under torsional loading (slope =0.92), the opposite was true for axial (slope = 1.14 (intact) 1.24 (implanted)) and bending (slope = 1.06) loads. This is probably due to a discrepancy in the material properties of the model.
Human articular cartilage samples were retrieved from the resected material of patients undergoing total knee replacement. Samples underwent automated controlled freezing at various stages of preparation: as intact articular cartilage discs, as minced articular cartilage, and as chondrocytes immediately after enzymatic isolation from fresh articular cartilage. Cell viability was examined using a LIVE/DEAD assay which provided fluorescent staining. Isolated chondrocytes were then cultured and Alamar blue assay was used for estimation of cell proliferation at days zero, four, seven, 14, 21 and 28 after seeding. The mean percentage viabilities of chondrocytes isolated from group A (fresh, intact articular cartilage disc samples), group B (following cryopreservation and then thawing, after initial isolation from articular cartilage), group C (from minced cryopreserved articular cartilage samples), and group D (from cryopreserved intact articular cartilage disc samples) were 74.7% (95% confidence interval (CI) 73.1 to 76.3), 47.0% (95% CI 43 to 51), 32.0% (95% CI 30.3 to 33.7) and 23.3% (95% CI 22.1 to 24.5), respectively. Isolated chondrocytes from all groups were expanded by the following mean proportions after 28 days of culturing: group A ten times, group B 18 times, group C 106 times, and group D 154 times. This experiment demonstrated that it is possible to isolate viable chondrocytes from cryopreserved intact human articular cartilage which can then be successfully cultured.
Anteromedial osteoarthritis is a distinct phenotype of osteoarthritis. The arthritic lesion on the tibia is localised to the anteromedial quadrant with an intact ACL. Deficiency of the ACL leads to a progression to tricompartmental disease. Within the spectrum of intact ACL a varying degree of ligament damage is seen. Our aim was to correlate the progression of ACL damage to the geographical extent of disease and the degree of cartilage loss on the tibial plateau. We systematically digitally mapped 50 tibial plateau resection specimens from clinical photographs of patients undergoing unicompartmental arthroplasty, additionally the damage to their ACL was graded (0: normal, 1:synovium loss, 2:longitudinal splits) These images were imported into image analysis software. Accurate measurements were made of the dimensions of the specimen. Measurements included the AP distance to the anterior and posterior aspect of the lesion, and the distance to the start of the macroscopically non damaged cartilage. The areas of cartilage damage and full thickness loss were also recorded. The results were represented as a % of total area to account for variation in size of the resection specimens. We compared % of full thickness loss in patients with normal to those with damaged, but functionally intact ligaments. All specimens had a similar macroscopic appearance. A significant difference was seen with the progression of ACL damage and area of eburnation of bone. Using an unpaired t test, a significant difference in area of % full thickness cartilage loss (P=0.047) was seen between patients with a normal and longitudinal splits within their ACL. No correlation between the clinical status of the ACL and start or finish point of cartilage loss on the tibial plateau We surmise that the progression from anteromedial to tricompartmental osteoarthritis of the knee may be related to the graduated damage of the ACL.
A sibling risk study that shows a statistically significant increase in risk for anteromedial osteoarthritis of the knee. Anteromedial osteoarthritis is a distinct phenotype of osteoarthritis. Previous studies have shown a genetic aetiology to both hip and knee osteoarthritis. The aim of this study was to determine the sibling risk of antero-medial osteoarthritis of the knee. We conducted a retrospective cohort study of 132 probands with primary anteromedial osteoarthritis, who had undergone unicompartmental arthroplasty. Sibling were identified as having symptomatic knee problems by postal Oxford Knee Score (OKS). A positive OKS was defined as an OKS+/− 2SD of the mean of the proband group. Sibling spouses were used as controls. Those siblings &
spouses that were symptomatic from the OKS were invited to undergo Knee X-rays, to look for radiological signs of osteoarthritis. Osteoarthritis was diagnosed as greater than Grade II on the Kell-gren Lawrence classification. The pattern of disease was noted and it was considered if the sibling were suitable for a unicompartmental knee arthroplasty. The prevalence and sibling risk of anteromedial osteoarthritis was determined using a randomly selected single sibling per proband family. The prevalence was determined in the 103 single proband sibling pairs. There was a statistically significant risk within the sibling group P= 0.024 using the Chi square test. The relative risk of anteromedial osteoarthritis was. 3.21(95% CI 1.08 to 9.17) Genetic factors play a major role in the development of anteromedial osteoarthritis.
Wear debris is a key factor in the pathophysiology of aseptic loosening of orthopaedic endoprostheses. Cobalt-chromium-molybdenum (Co-CrMo) alloys are used for metal-metal hip implants due to their enhanced wear resistance profiles. Whilst these alloys have widespread clinical application, little is known about their direct effect on osteoblast biology. To address this issue, in this study we have investigated particle-mediated inflammation, as a putative mechanism of aseptic loosening. The effects of Co2+ ions on the bone cellular milieu were assessed in vitro by profiling of classical inflammatory mediators. The inflammatory driver PGE2 was quantified and found to be increased, following osteoblast stimulation with metal ions, suggesting the initiation of a local inflammatory response to metal particle exposure. To determine the biological import of this molecular event, the role of metal ions in recruiting inflammatory cells by chemokine production was assessed. These data demonstrated significant induction of the chemokines, IL-8 and MCP-1 following both 12 and 24 hour exposure to 10ppm of Co2+. In this study, we demonstrate that Co2+ particles can rapidly induce chemotactic cytokines, IL-8 and MCP-1 early stress-responsive chemokines that function in activation and chemotaxis of monocytes, and PGE2, which stimulates bone resorption. We have shown that this induction occurs at a transcriptional level with significantly increased mRNA levels. These data lend further weight to the hypothesis that wear mediated osteolysis, is due, at least in part, to underlying chronic inflammation.